It is a glimmer of hope for treating glioblastoma, the most aggressive brain tumor. A team from the University of Florida has announced that it has developed a therapeutic messenger RNA (mRNA) vaccine. Admittedly, this trial only involves four adult patients, but the results, the fruit of seven years of research, seem very promising. They were published in the review cell on May 9.
The principle of the vaccine of the team led by Elias Sayour, pediatric oncologist at the university’s cancer center, is the same as that used for Covid-19 or currently being tested to prevent recurrence of cancer (melanoma, pancreas, lung ): induce an immune response and let the body fight the disease itself. In this study, the patient’s own tumor cells were used to create a personalized vaccine.
However, American researchers have innovated for the “dressing” of the vaccine. Indeed, to be effective, the mRNA contained in the vaccine must be protected. For the one against Covid-19, it is thanks to a lipid nanoparticle, a sort of protective shell which allows the mRNA to better enter the cells. In the University of Florida clinical trial, the mRNA was wrapped in several layers of particles of the same nature, which wrap around each other, forming a sort of onion. “These layers alert the immune system in a much more powerful way than single particles would. Results from the dog trial showed that the vaccine reprogrammed the tumor microenvironment within days, allowing activated cells of the immune system to fight the tumor.explains Elias Sayour.
A very robust response
This is another originality of this work. The team tested its vaccine on mice, but also, and this is rather rare, on ten pet dogs which had spontaneously developed glioblastoma and for which there was no therapeutic option.
Whether in mice, dogs or humans, the immune response was very robust. In less than forty-eight hours, Elias Sayour claims to have seen with surprise the tumor or the tumor environment go from “cold” (with few immune cells) “hot”, that is to say with inflammatory cells. The latter respond to immunotherapy, unlike “cold” tumors.
American researchers highlight a mechanism that is also innovative. Normally, to induce a good immune response, RNA vaccines seek to target dendritic cells – key to the immune system, they are supposed to alert, in the event of danger, the other cells of the immune system to induce the production of antibodies. However, the vaccine tested here does not target dendritic cells but those of the stroma (non-tumor tissue naturally present in organs, and in all types of invasive cancers – except leukemia). ” It’s very original. It may be a new way to stimulate an immune response after the administration of these anti-cancer vaccines but, as it does not correspond at all to classic dogma, it raises questions., notes Eric Tartour, immunologist at the Georges-Pompidou European Hospital, in Paris. The latter does not hide a certain enthusiasm: “It is not every day that a new RNA vaccine platform is proposed with mechanisms different from what we are used to seeing, but we will have to confirm all these new mechanisms of action . »
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